Cardiac resynchronization therapy: variations in echo-guided optimized atrioventricular and interventricular delays during follow-up.

BACKGROUND: Relatively few data are available on long-term echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay programming in cardiac resynchronization therapy (CRT). We assessed variations in optimized AV and VV delays during long-term follow-up. METHODS: Thirty-seven consecutive heart failure patients received Doppler echocardiographic optimization of AV and VV delay within 48 hours from CRT device implantation, at 6 months and at 12 months (the last for the first enrolled 14 patients). RESULTS: After implantation, median optimized AV delay was 100 ms (range, 45 ms); VV optimization led to simultaneous biventricular activation in 4 patients, left ventricular preactivation in 17 patients and right ventricular preactivation in 16 patients. At 12 months median AV delay decreased to 85 ms (23 ms) (P < 0.05 vs. baseline). With respect to previous assessment, VV delay variations > or =40 ms were observed in 41% of the patients at 6 months and in 57% of the tested patients at 12 months. A nonconcordance (by Kappa test) of optimized VV delays was found between each new assessment and the previous one. VV delay optimization was associated with significant (P < 0.001) increases in aortic velocity time integral both at baseline and during follow-up. CONCLUSIONS: Echocardiographic optimization of AV and VV delay is associated with broad intraindividual variability during follow-up. A new assessment of optimized VV delays during long-term follow-up reveals a nonconcordance with previous values and provides increases in forward stroke volume.

Matrix metalloproteinases in premature coronary atherosclerosis: influence of inhibitors, inflammation, and genetic polymorphisms.

Matrix metalloproteinases (MMPs) are thought to participate in the pathogenesis of coronary artery disease (CAD), particularly in the occurrence of acute coronary syndrome (ACS). Little is known about human in vivo MMP regulation in CAD. The expression and regulation of MMPs and their tissue inhibitors (TIMPs) were evaluated in premature CAD. The distribution of MMP-3 5A/6A and MMP-9 C/T promoter polymorphisms and MMP-9 A/G exon-6 polymorphism were investigated in 200 consecutive male premature CAD patients (aged < or = 55 years) and 201 age-matched male blood donors. Plasma concentrations/activities of MMP-2 and MMP-9 were also measured, as were plasma concentrations of MMP-3, TIMP-1, and TIMP-2 in 80 patients (49 with ACSs and 31 with stable CAD) and 40 controls. Inflammation markers were also obtained. MMP genetic polymorphism distributions did not vary between patients and controls and did not seem to influence their respective MMP plasma levels. Patients showed increased MMP-9 and TIMP-1 concentrations and decreased TIMP-2 concentration and MMP-2 total activity (all P < or = 0.002). Overall, TIMP-1 correlated with C-reactive protein (CPR) (r = 0.594, P < 0.001) and haptoglobin (r = 0.276, P = 0.005), whereas MMP-2 activity correlated inversely with haptoglobin (r = -0.195, P = 0.032). Blood glucose correlated positively with TIMP-1 concentration (r = 0.711, P < 0.001) and negatively with MMP-2 activity (r = -0.250, P = 0.006). In conclusion, MMP and TIMP plasma levels in premature CAD are linked to clinical presentation and markers of inflammation and metabolic disorders rather than to genetic polymorphisms.

Neurohormones and inflammatory mediators in patients with heart failure undergoing cardiac resynchronization therapy: time courses and prediction of response.

Despite interest in neurohormonal activation as a determinant of prognosis in chronic heart failure (CHF) and as a target for pharmacological treatments, data are lacking on the time-related effects of electrical cardiac resynchronization therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this study was to assess time-courses and extents of changes within the neurohormonal profile of CHF patients treated with CRT. We performed a prospective follow-up study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT on a broad panel of neurohormones proposed for characterization of CHF patients. Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine, norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3 months of CRT; when feasible, measurements were also performed at 1 week, 1 month and 12 months (clinical evaluation, echocardiography and ECG were also performed at each time-point). The results showed that at 3 months improvement in NYHA class and echographically assessed left ventricular (LV) reverse structural remodeling were accompanied by significant reductions versus baseline in ANP and BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or = 150 pg/ml was a good predictor of response to CRT in terms of NYHA class reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly reduce natriuretic peptides concentrations, while values of other neurohormones and inflammatory cytokines are relatively unvaried. A baseline ANP concentration < or = 150 pg/ml might be a clinically useful predictor of medium-term response to CRT.

Acute and chronic haemodynamic effects of biventricular pacing and of switching to different pacing modalities in heart failure patients.

BACKGROUND: In patients with severe heart failure, sinus rhythm and wide QRS complex biventricular (BiV) pacing leads to clinical and haemodynamic improvement, but the immediate reversibility of these changes is not known. METHODS: We assessed the acute and medium-term (3-month) haemodynamic effects of BiV pacing and of switching to other pacing modalities in 21 patients with severe heart failure, sinus rhythm and QRS>or=130 ms. Haemodynamic studies were performed: 1) at the time of implantation of a BiV pacing device, during AAI pacing, atrial synchronous right ventricular (RV) pacing, atrial synchronous left ventricular (LV) pacing and atrial synchronous BiV pacing (all at 100 bpm); 2) after 3 months of continuous BiV pacing--with evaluations being made by switching to RV and the other pacing modalities. RESULTS: At both the acute and medium-term evaluations, BiV pacing provided the greatest improvement in cardiac index. Switching from BiV to RV pacing led to a more marked decrease in the cardiac index at 3 months. No strict correlation was evident between acute and medium-term effects of BiV pacing on cardiac index. CONCLUSION: Cardiac resynchronization by BiV pacing provides acute/medium-term improvements in cardiac index. Sudden, medium-term failure of LV stimulation can lead to an even more pronounced haemodynamic derangement than that inducible by RV pacing at baseline. Acute haemodynamic evaluations do not seem to provide a powerful way for identifying medium-term responders.

Increase in QT/QTc dispersion after low energy cardioversion of chronic persistent atrial fibrillation.

BACKGROUND: The effects of atrial internal cardioversion on QT interval and QT dispersion (parameters associated with increased risk of ventricular tachyarrhythmias) are unknown. We investigated changes in QT interval, QTc and QT dispersion immediately after shock delivery for internal cardioversion in patients with chronic persistent atrial fibrillation. METHOD: Twenty-two patients with chronic persistent atrial fibrillation (mean duration, 17+/-23 months) underwent transvenous low-energy internal atrial cardioversion with a step-up protocol of shocks delivered between catheters in the right atrium and coronary sinus. (successful shock, 7.2+/-4.2 J). RR interval, QT interval, QTc interval, QT dispersion, and QTc dispersion were all measured on three consecutive beats (at 75 mm/s on at least 9 of 12 leads) and then averaged both before and after (1) the last unsuccessful shock, and (2) sinus rhythm restoration. RESULTS: All parameters remained similar in the minute before and after the last unsuccessful shock. At 1 min after the successful shock, abrupt increases in QT dispersion (+43.8% vs. pre-shock; P<0.001 at least significant difference analysis) and QTc dispersion (+30.0%; P<0.05) were observed, followed by a gradual return to pre-shock values at 15 min. CONCLUSIONS: These findings strongly suggest the likely existence of a brief period of increased electrical vulnerability immediately after restoration of sinus rhythm by internal cardioversion. Particular caution should therefore be applied whenever class III antiarrhythmic drugs are administered immediately after successful internal atrial cardioversion.

Late improvement in ventricular performance following internal cardioversion for persistent atrial fibrillation: an argument in support of concealed cardiomyopathy.

The aim of the study was to evaluate the time course of atrial and ventricular function improvement following internal atrial cardioversion in patients with structural heart disease. Twenty-nine patients with chronic persistent atrial fibrillation (AF) and underlying structural heart disease were followed by serial echocardiograms performed at 1 and 6 hours, 1 day, 1, 2, and 3 weeks, and 1, 2, 3, and 6 months after successful cardioversion. Sinus rhythm was maintained at 6 months in 24 patients. Following cardioversion the time course of left atrial mechanical function (peak A wave, percent A wave filling) differed from that of left ventricular ejection fraction: peak A wave values (cm/s) increased significantly at 1 week (51 +/- 23 vs 35 +/- 15 at 1 hour, P < 0.05), percent A wave filling (%) increased significantly at 2 weeks (34 +/- 12 vs 22 +/- 9 at 1 hour, P < 0.05), whereas left ventricular ejection fraction (%) increased later (at 1 month 60 +/- 14 vs 55 +/- 14 at baseline, P < 0.05 and at 2 months 60 +/- 14 vs 56 +/- 14 at 1 hour, P < 0.05). In conclusion, restoration of sinus rhythm results in an improvement in left ventricular ejection fraction during follow-up, even in patients with structural heart disease without fast ventricular rates at baseline. The dissociation between the time course of atrial and ventricular function improvement suggests that the latter was partly due to regression of a concealed form of cardiomyopathy and/or of a ventricular dysfunction due to chronic AF.

Transvenous internal cardioversion for atrial fibrillation: a randomized comparison between catheters with different coil length.

OBJECTIVES: The aim of this study was to evaluate the effects of 2 different right atrial electrode coil lengths on energy and voltage requirements for transvenous atrial cardioversion. METHODS: Twenty-six patients (mean age 61 +/- 11 years) with chronic persistent atrial fibrillation (AF) (mean duration 11 +/- 10 months) underwent transvenous cardioversion. A 6F catheter with a 5.5-cm coil was positioned in the coronary sinus. Another catheter with either a 5.5-cm or an 8-cm coil was positioned along the lateral wall of the right atrium, according to a randomized allocation. R wave-synchronized biphasic shocks were delivered according to a step-up protocol. After cardioversion of baseline AF, AF was reinduced, the right atrial catheter was substituted, and cardioversion was repeated with the alternative right atrial coil. RESULTS: Successful cardioversion was obtained in all of the patients. Leading edge voltage of effective shocks was significantly lower when catheters with an 8-cm coil in right atrium were used compared with the alternative 5-cm coil catheters (301 +/- 80 volts vs 340 +/- 78 volts, P <.001), and delivered energy (6.75 +/- 4.25 joules vs 7.86 +/- 4.29 joules, P =.043) and shock impedance (60 +/- 9 ohm vs 66 +/- 10 ohm, P <.001) were lower. Moreover, shock-induced discomfort, evaluated by assessment of pain score, was reduced (3.69 +/- 1.09 vs 4.12 +/- 0.99, P =.035). CONCLUSIONS: The use of a longer right atrial coil results in lower shock impedance, lower energy and voltage requirements, and lower discomfort during transvenous atrial cardioversion. The results of the current study are of value either for transvenous internal cardioversion of chronic persistent AF or for implantable atrial defibrillators.

A randomised cross-over study on the haemodynamic effects of oral dofetilide compared with oral sotalol in patients with ischaemic heart disease and sustained ventricular tachycardia.

OBJECTIVE: To assess the haemodynamic effects of short-term treatment with dofetilide in comparison with sotalol in patients with ischaemic heart disease. METHODS: Twelve patients with ischaemic heart disease and sustained ventricular tachycardia were treated with dofetilide [500 microg twice daily (b.i.d.)] or sotalol (160 mg b.i.d., randomised sequence separated by wash-out period) for 3-5 days. Right-heart catheterisation was performed at baseline and at the end of each short-term treatment phase. RESULTS: The main findings were a significant reduction in heart rate, mean systemic pressure and cardiac index (-13%) during treatment with sotalol. Conversely, cardiac index increased significantly during dofetilide (mean percentage change 11%) with no effect on heart rate and systemic blood pressure. CONCLUSIONS: Oral dofetilide exerts favourable haemodynamic effects in comparison with D,L-sotalol following short-term oral treatment. In view of these observations, the use of dofetilide may be proposed also in patients with ventricular tachyarrhythmias associated with impaired left-ventricular function. Whether the haemodynamic differences between dofetilide and D,L-sotalol are the basis for differences in tolerability remains to be evaluated.